The long-term objectives of this project are to assist in the solution of problems of hypertension, shock, and circulatory failure. A multidisciplined approach will be utilized by a team of experts which has already been assembled and which has been working together in a coordinated and productive manner. The endocrine, neurohumoral, hemodynamic, vascular, renal, and prenatal factors involved in hypertension and circulatory failure will be studied intensively. The studies will include examination of the basic molecular biochemistry and physiology of the circulation, the pathophysiology of these diseases in man and experimental animal models, and the experimental therapy of these disorders. The studies should help clarify the normal and abnormal mechanisms affecting the blood pressure and circulation and contribute to the development of improved forms of treatment for major circulatory diseases.